Over a million Americans experience a myocardial infarction (heart attack) each year. Following a heart attack, damaged heart muscle cannot regenerate; instead, it is gradually replaced by scar tissue over the course of several weeks. The loss of heart muscle reduces the ability of the heart to pump blood, and in many cases this triggers a gradual decline in heart function and alterations in heart size and shape (remodeling) that ultimately lead to heart failure. Although drugs such as angiotensin converting enzyme (ACE) inhibitors can help reduce post-infarction remodeling, the risk of developing heart failure after surviving a heart attack remains high. Because the mechanical properties of the scar tissue that forms after a heart attack are critical determinants of both heart function and the eventual transition to heart failure, several new therapies under development attempt to modify the mechanical properties of that scar in order to reduce left ventricular (LV) remodeling, improve pump function, or both. Recent computer modeling and experimental studies suggest that infarcts that are very stiff in one direction but relatively soft in others (mechanically anisotropic) should provide the best heart function. This proposal focuses on a novel method to create mechanical anisotropy by surgically reinforcing the infarct. Based on preliminary data showing that anisotropic reinforcement dramatically improves pump function immediately after a heart attack, this project will test the hypothesis that anisotropic reinforcement reduces LV remodeling and functional deterioration over the first 2 months following myocardial infarction in a large animal model. New computational modeling studies will also determine whether infarcts in different locations require different patterns of mechanical reinforcement to optimize LV function. PUBLIC HEALTH RELEVANCE: Over a million Americans experience a myocardial infarction (heart attack) each year. After surviving a heart attack, many patients experience a gradual decline in heart function and alterations in heart size and shape (remodeling) that ultimately lead to heart failure. The goal of this work is to test the ability of an innovative new therapy that improves heart function early after a heart attack to reduce subsequent functional deterioration and remodeling.